Food for Thought Diet, BMI & MS? - IOMSN

Food for Thought Diet, BMI & MS?

Aliza Ben-Zacharia, DrNP, ANP The Corinne Goldsmith Dickinson Center for MS

The Ichan School of Medicine at Mount Sinai

Main Questions in MS & Diet/BMI

Is a high BMI is associated with developing MS?

Is a high BMI associated with MS progression?

Is there any association between diet & MS?

Is there association between the microbiome, the diet in MS & the progression of MS?

You Are What You Eat!

“Let food be thy medicine and medicine be thy food” Hippocrates

1826 - Anthelme Brillat-Savarin "Dis-moi ce que tu manges, je te dirai ce que tu es.” - Tell me what you eat and I will tell you what you are

1863 - Ludwig Andreas Feuerbach wrote: "Der Mensch ist, was er ißt.” 'man is what he eats’

Body Mass Index (BMI) – > 25 & 30

High BMI/Obesity & Development of MS

Objective: To examine whether obesity during childhood, adolescence, or adulthood is associated with an increased risk of MS

Methods

Women in the Nurses’ Health Study (n 121,700) and Nurses’ Health Study II (n 116,671) provided information on weight at age 18 and weight and height at baseline, from which body mass index was derived

Women selected silhouettes representing their body size at ages 5, 10, and 20

Over the total 40 years of follow-up in both cohorts combined, we confirmed 593 cases of MS

Statistical models, adjusting for age, latitude of residence, ethnicity, and cigarette smoking, were used to estimate the rate ratios and 95% confidence intervals (CI).

Munger et al. Neurology® 2009;73:1543–1550

Nine silhouettes women selected to best describe their body size at ages 5, 10, and 20


Those who were obese by age 18 had double the risk for MS - These illustrations represent a BMI of 30 or more


Nurses’ Health Study (n 121,700) & Nurses’ Health Study II (n 116,671)

Obesity at age 18 (body mass index 30 kg/m2) was associated with a greater than twofold increased risk of MS as compared to women with a BMI between 18.5 and 20.9 kg/m2

MS risk among women who were overweight, but not obese, at age 18 (BMI 25–29.9 kg/m2) was only moderately increased Obese adolescents have an increased risk of developing multiple sclerosis (MS)

The mechanisms of this association is uncertain, but this result suggests that prevention of adolescent obesity may contribute to reduced MS risk


Obesity & Risk of MS – Nurses’ Study


Relative Risk of Multiple Sclerosis for Body Mass Index at Age 18 Years

Body Mass Index, kg/m2 Multivariate-Adjusted Relative Risk (95% CI)

<18.5 0.96 (0.73 – 1.27)

18.5 – <21 1 [Reference]

21 – <23 1.13 (0.91 – 1.40)

23 – <25 0.97 (0.72 – 1.31)

25 – <27 1.44 (0.87 – 2.39)

27 – <30 1.40 (0.92 – 2.14)

>30 2.25 (1.50 – 3.37)

CI = confidence interval


Nurses’ Health Study (n 121,700) & Nurses’ Health Study II (n 116,671)

Women with a BMI 30 kg/m2 at age 18 had a 71% increased risk of MS as compared to women with BMI between 18.5 and 20.9 kg/m2

As smoking was the main confounder of the association between obesity at age 18 and MS risk, we also restricted analyses to never smokers in the NHSII (there were too few never smokers in the NHS cohort to do a comparable analysis);

The twofold increased risk of MS persisted among never smoking women with a BMI at age 18 30 kg/m2 (RR 2.34, 95% CI 1.21– 4.53, p 0.01)

BMI & Developing MS

In a Swedish population-based case-control study (1571 cases, 3371 controls), subjects with different BMIs were compared regarding multiple sclerosis (MS) risk, by calculating odds ratios (OR) with 95% confidence intervals (95% CI)

Subjects whose BMI exceeded 27 kg/m(2) at age 20 had a two-fold increased risk of developing MS compared with normal weight subjects

The obesity epidemic may explain part of the increasing MS incidence as recorded in some countries. Measures taken against adolescent obesity may thus be a preventive strategy against MS

Hedström et la., Multiple Sclerosis, 2012 Sep;18(9):1334-6

BMI & Progression of MS

OBJECTIVES:

To assess the potential of an online platform, PatientsLikeMe.com (PLM), for research in multiple sclerosis (MS)

The role of body mass index (BMI) on MS disease course was conducted to illustrate the utility of the platform

METHODS:

Compared the demographic characteristics of subjects from PLM and from a regional MS center

Validated PLM's patient-reported outcome measure (MS Rating Scale, MSRS) against standard physician-rated tools

Analyzed the relation of BMI to the MSRS measure

Bove et. Al., PLoS One. 2013;8(3):e59707.

BMI & Progression of MS - Results

Compared with 4,039 MS Center patients, the 10,255 PLM members were younger, more educated

Disease course RRMS, with younger symptom onset and shorter disease duration.

MSRS scores for 121 MS Center patients revealed acceptable agreement between patient-derived and physician-derived composite scores (weighted kappa = 0.46). The Walking domain showed the highest weighted kappa (0.73) and correlation (rs = 0.86) between patient and physician scores.

Using PLM data, a modest correlation between BMI and cross-sectional MSRS (rho = 0.17) and no association between BMI and disease course

Bove et. Al., PLoS One. 2013;8(3):e59707.

What is a Healthy Diet for MS?

Swank Diet?

Dairy food?

Vegetarian?

Paleo Diet?

Mediterranean Diet??

Low saturated fat diet?

Gluten Free Diet?

All Raw? Even Lisa is confused!

Dietary Key Points

Dietary changes & supplements are used by patients with MS without reliable evidence for their risks & benefits

Low vitamin D is associated with a worse course of disease in observational studies

Polyunsaturated fatty acids & a low fat diet attenuate MS immune responses in vitro & in animal studies but limited data in MS

Antioxidants, probiotics & vitamin B 12 supplementation attenuate MS immune response in vitro & animal models but limited data in humans

Milk proteins & Gluten are thought to worsen the outcomes in MS, but no randomized controlled trials re dietary restrictions

Von Gelden & Mowry, Nature Review Neurology, 2012, 8, 678-689.

Swank Low Saturated Fat Diet

144 patients with MS – DSS 4-5, ambulatory but with difficulty – fatigue & low endurance – all had ~124 g/d saturated fat

70 patients – low fat diet – 20 g/d saturated fat – “Good Dieters” - overall fat consumption 16± 2.8 g/d

74 patients with MS - >20 g/d saturated fat – “Poor Dieters” – overall fat consumption 38 ± 18 g/d

Followed frequently initially = visits & then Phone FU

Swank & Goodwin, Nutrition, 2003, 19:161-162.


Followed for 34 years

23 deaths - 14 (20%) due to MS – in “Good Dieters”

58 deaths - 48 (61%) due to MS – in “Poor Dieters”

63 surviving patients continued the study up to 50 years

2000 – 15 patients were seen who started the study 1950s

15 patients ages 72 – 84 year old – 13 ambulatory & care for themselves & 2 with difficulty walking



Low fat diet proposed by Swank – 10-15 g/d of saturated fat during 50 years study

20% of patients with MS on the lowest fat diet showed little or no neurologic deterioration as a result of the progress of the disease

Higher percentage than the 4% of “Mild MS” cases expected within a large group of patients


Low Saturated Fat Diet

Restriction of saturated fat induces remission of the disease & produces beneficial effects in MS patients

Saturated fat decrease membrane fluidity, lead to the synthesis of cholesterol, activate the CD14/TLR4 leading to formation of TNF-α

Fat influences transcriptional level, gene expression, cell metabolism & cell growth & differentiation

Swank & Goodwin, Nutrition, 2003, 19(5), 478 Jump & Clarke, Annual Review of Nutrition, 1999, 19, 63-90.

Essential Fatty Acids & MS

Ω-3 (α-linoleic fatty acid) – fish oil & Ω-6 (linoleic fatty acid) – plants

Hypothesis: Diet high in meat & dairy & low in fish increases the risk of MS

Swank 1950 – Norway – higher incidence of MS among those that had high consumption of animal fat & dairy products than fish consumption

No association between animal fat or saturated fat & the risk of MS – case control studies

Swank et al. NEJM, 1952, 246, 721. Antonovsky et al. Arch. Neurolgy, 1965, 13, 183

Essential Fatty Acids & MS

Prospective cohort study

The amount & type of dietary fat did not affect the risk of developing MS

Ω-3 (α-linoleic fatty acid) was associated with a reduced risk of MS but it did not reach statistical significance

No significant association between fish consumption & MS risk in one case control study but fish consumption was significantly associated with a reduced risk of MS in women

Zhang et al., Am J Epidemiology, 2000, 152, 1056. Ghadirian et al., J. Epidemiology, 1998, 27, 845

Polyunsaturated Fatty Acids (PUFA)

Nordvik – fish oil supplements & progression of MS in 16 newly diagnosed patients – significant reduction in relapse rate and improvement on EDSS

Weinstock-Guttman – low fat diet supplemented with Ω-3 PUFA has moderate benefits in RRMS but the potential therapeutic effects may be related to the low fat diet

Increased intake of Ω-3 fatty acids reduce the synthesis of pro-inflammatory leukotriene B4 and prostaglandin E2

Nordvik et al., Acta Neurol Scand. 2000, 102, 143. Weinstock-Guttman et al., Prostaglandins Leukot. Essent. Fatty Acids, 2005, 73, 397. Calder P.C. Trends Immunol. Today, 1998, 6, 244. James et al., Am J. Clin. Nutr., 2000,71, 343S.

Omega-3 Fatty Acids

There is evidence that omega-3 fatty acids reduce the risk of cardiovascular events

There is not enough definite proof available to recommend omega-3 fatty acids for MS, but findings suggest beneficial effects from unsaturated fatty acids

Justifiable to consume foods rich in omega-3 fatty acids, high-quality vegetable oils (containing high amounts of unsaturated fats), and 2 or more seafood meals per week

Schwarz S, Leweling H. Multiple sclerosis and nutrition. Multiple Sclerosis. 2005;11:24–32.

Consumption of milk & MS

High consumption of milk was associated with increased incidence of MS

The incidence of MS in Japan rose between the years 1950 – 1969 in parallel with increased consumption of milk

Meat & dairy products were associated with incidence of MS in the USA

Schwarz & Leweling, Multiple Sclerosis, 2005, 11, 24-32. Butcher. N Z Medicine J, 1976, 83, 427-430.

Cow Milk – Saturated Fat

Milk proteins with effect in MS are the proteins of the milk fat globule membrane (MFGM proteins)

The most representative of MFGM is Butyrophilin (BTN)

BTN is similar to MOG (myelin oligodendrocyte glycoprotein)

BTN blocks MOG-induced EAE but also induces inflammatory responses in the CNS

Antibody cross-reactivity between MOG & BTN has been observed in MS

Riccio et al., Autoimmune Diseases, 2010.

Gluten Free Diet & MS

Open label trial

End Points: ARR, EDSS

42 patients on a gluten free diet

Results

No change in relapse rate

No change in disease progression based on EDSS

Liversedge, L. British Medical Bulletin, 1977, 33, 78-83.

Paleo Diet Food Pyramid

Vitamin D & MS

Studies indicate that vitamin D alters immune function in a way that may be desirable in MS

Many people with MS have risk factors for developing osteoporosis:

Female gender, decreased physical activity, decreased exposure to sunlight, and frequent treatment with steroids

People who have these risk factors may consider supplements of vitamin D and calcium

Recommended intake of vitamin D is based on blood test level

Schwarz S, Leweling H. Multiple sclerosis and nutrition. Mult Scler. 2005;11:24–32.

Vitamin D & MS

Double blind placebo controlled randomized trial

End Points: ARR, EDSS,MSFC

35 patients received vitamin D3 20,000 IU weekly vs. 33 patients getting placebo

Results

No change in relapse rate or EDSS score

Kampman et al., Multiple Sclerosis, 2012, 18, 1144-1451.

Vitamin D - Nurses’ Study

Nurses’ Health study (20yrs) and Nurses’ Health study II (10yrs) –

40% reduced risk of MS found in women in the highest quintile

of vitamin D intake compared with those in the lowest quintile

Vitamin D supplementation showed correlation with increased

risk of development of MS

Vitamin D deficiency may lead to increased intensity of the

symptoms in MS due to enhancement of inflammatory

cytokines

Polymorphisms in certain genes for the vitamin D receptor have

been associated with increased likelihood of MS

Vitamin B12 & MS

Vitamin B12 is a prerequisite for the synthesis of myelin

Vitamin B12 & MS share clinical & MRI characteristics

High dose therapy with vitamin B 12 over 6 months trial in 6 severely disabled patients with MS – no clinical benefit

Placebo control trial with 138 patients – small without significance - beneficial effect of parenteral therapy of vitamin B12

No scientific basis to recommend vitamin B12 supplementation unless has deficiency

Schwarz & Leweling, Multiple Sclerosis, 2005, 11, 24-32. Kira et al., Internal Medicine, 1994,33, 82-86. Wade et al., J neurol Neurosurg Psychiatry 2002, 73, 246-249.

Probiotics & MS

Open label single blind trial

Primary end point: Gadolinium enhancing lesions on MRI

Secondary end point: serum cytokine levels (IL4, IL10, IL17)

Results:

RRMS - naive patients - Decreased numbers of lesions on GAD MRI as compared to pre study

Increased levels of IL4 & IL10

Administration of probiotics to Mice EAE model

Reduction in IL 17 & increased IL10

Von Gelden & Mowry, Nature Review Neurology, 2012, 8, 678-689.

Uric Acid – BBB Integrity

Study Design: Double blind placebo controlled randomized – 16 patients with RRMS taking inosine for 12 months vs. 6 months of placebo followed by 6 months of inosine

End Points: RR, EDSS, MRI

Results:

Decreased number of Gad enhanced lesions seen on MRI

Decreased EDSS score

Markowitz et al., J Alternative Complementary Medicine, 2009, 15, 619-625

Uric Acid & MS

Study Design: Multicenter - Double blind placebo controlled randomized – 159 patients – inosine vs. placebo as add on to IFN-β

End Points: Primary: change in EDSS at 24 months

Secondary: time to confirmed disability progression, time to first relapse, mean EDSS change, ARR, MSFC & number of relapses

Results: No change in in relapse rate No change in EDSS scores

Gonsette et al., Multiple Sclerosis, 2010, 16, 455-462.

2 Cochrane Review – 2012

Attempt to answer patients’ questions about dietary recommendations and their impact of prognosis for people with MS

Selection criteria limited to MS and trials that had a comparison arm

Results:

No specific recommendation for diet & supplements – adopt healthy eating habits

PUFAs seem to have no effect on disease progression & the risk of clinical relapses over 2 years

Low level of vitamin D is associated with lower subsequent disability – authors noted no cause-effect relationship

Farinotti et al., Cochrane Database Syst Rev. 2007 Jan 24;(1):CD004192.

Dr. Sergio Baranzini – Microbiome Project / UCSF MS EPIC Study

Relationship between Microbiome, Diet & MS

The link between dietary intake and host immune system is not direct, but mediated by the commensal bacteria residing in the walls of the intestine called the microbiome

Commensal bacteria can be classified based on their unique DNA sequences

Commensal bacterial – responsive for dietary manipulations, regulating metabolism, nutrient absorption and modulation of immune activity

The importance of the intestinal microbiome & its interactions with the immune system are recognized with regard to the development of autoimmune diseases

http://blog.mountsinai.org/blog/exploring-the-role-of-microbiome-in-multiple-sclerosis/
















Known Core & Number of Species

Lactobacillus lactis 1

Lachnobacterium spp. 1

Lachnospira pectinoschiza 1

Parabacteroidesspp. 3

Prevotella spp. 2

Roseburia intestinalis 1

Ruminococcus spp. 13

Streptococcus spp. 18

Subdoligranulum variabile 1

Sutterella wadsworthia 1

Uncultured Phylotypes 387

Akkermansia muciniphila 1

Alistipes finegoldii 1

Anaerotruncus colihominis 1

Bacteroides spp. 11

Bifidobacterium spp. 2

Clostridium spp. 13

Colinsella spp. 2

Dorea spp. 2

Eubacterium spp. 9

Faecalibacterium prausnitzii 1

Diet & Microbiome effects on MS

Rise in the incidence of Japanese patients developing RRMS was associated with ‘‘Westernized’’ dietary habits

EAE models suggest that the gut flora contribute to the development of disease

Sterilization of the gut by treatment with a mixture of antibiotics reduced the severity of EAE

Kira et al. (1999) Changes in the clinical phenotypes of multiple sclerosis during the past 50 years in Japan. J Neurol Sci 166:53–57

Ochoa-Reparaz et al (2009) Role of gut commensal microflora in the development of experimental autoimmune encephalomyelitis. J Immunol 183:6041–6050

Microbiome & extra-intestinal autoimmune diseases

Kamada et al., Nature Reviews Immunology 13, 321-335 (May 2013)

Summary No specific diet has proven beneficial in MS

Principles of healthy diet

No basis for recommendations to avoid particular foods (e.g., alcohol, meat, wheat/gluten, coffee, animal fat, dairy products)

Low saturated fat

Fish or Omega 3 supplementation

Probiotics / Vitamin D

Schwarz S, Leweling H. Multiple sclerosis and nutrition. Multiple Sclerosis. 2005;11:24–32.

Thank You!

Questions / Comments

Documents

Food for Thought Diet, BMI & MS? - IOMSN